Identification of a Novel SLC8A1-ALK Fusion and Non-Canonical Expression Significantly Responding to ALK-TKIs in Lung Adenocarcinoma: A Case Report

Approximately 2–7% of patients with non-small cell lung cancer harbor anaplastic lymphoma kinase (ALK) rearrangement events. Of note, typical ALK actionable rearrangements are sensitive to treatment with tyrosine kinase inhibitors (TKIs). However, different types of ALK fusion influence the clinical outcomes of this therapeutic approach. Approximately 10–40% of patients with ALK-fusion positive non-small cell lung cancer do not response to ALK-TKI therapy. Therefore, it is important to accurately identify the types of ALK rearrangement for appropriate selection of clinical treatment. We find a strategy combining DNA-targeted next-generation sequencing with RNA reverse transcriptase-polymerase chain reaction and sequencing, besides fluorescence in situ hybridization and immunohistochemistry, may provide an effective and practical solution for correct identification of partner genes and fusion structures in the diagnosis of ALK rearrangements, particularly for non-canonical expression patterns of ALK fusion events. The combined approach may lead to more benefits for patients. READ ARTICLE

OncoTargets and Therapy DOI:10.2147/OTT.S319845

Authors: Xingyu Zhu, Yuqi He, Yin Wang,Yan Lei, Xiaoxing Su, Yifan Liu, Shuangxiu Wu, Zhengfu He

Treatment of Brain Metastases of Non-Small Cell Lung Carcinoma

Lung cancer is one of the most common malignant neoplasms. As a result of the disease’s progression, patients may develop metastases to the central nervous system. The prognosis in this location is unfavorable; untreated metastatic lesions may lead to death within one to two months. Existing therapies—neurosurgery and radiation therapy—do not improve the prognosis for every patient. The discovery of Epidermal Growth Factor Receptor (EGFR)—activating mutations and Anaplastic Lymphoma Kinase (ALK) rearrangements in patients with non-small cell lung adenocarcinoma has allowed for the introduction of small-molecule tyrosine kinase inhibitors to the treatment of advanced-stage patients. The Epidermal Growth Factor Receptor (EGFR) is a transmembrane protein with tyrosine kinase-dependent activity. EGFR is present in membranes of all epithelial cells. In physiological conditions, it plays an important role in the process of cell growth and proliferation. Binding the ligand to the EGFR causes ..... READ ARTICLE

International Journal of Molecular Science DOI:10.3390/ijms22020593

Authors: Agnieszka Rybarczyk-Kasiuchnicz, Rodryg Ramlau, and Katarzyna Stencel

Lorlatinib for advanced ALK and ROS1+ non-small cell lung cancer (NSCLC): Efficacy and treatment sequences in the IFCT-1803 LORLATU expanded access program (EAP) cohort

Background: Lorlatinib, a third-generation tyrosine kinase inhibitor targeting ALK and ROS1, has been made available in France starting October 2015 through an EAP for advanced, refractory, ALK+ NSCLC after the failure of chemotherapy and TKIs. Besides the landmark, multi-cohort phase II trial that assessed lorlatinib in ALK+ NSCLC, real-life evidence regarding the efficacy and safety, as well as treatment sequences including lorlatinib, is lacking. Methods: We report the cohort of consecutive patients with advanced, refractory, ALK or ROS1+ NSCLC enrolled in the French EAP of lorlatinib from October 2015 to October 2019. Data were collected from medical records by French Cooperative Thoracic Intergroup (IFCT) research study assistants on site. Primary endpoint was progression-free survival... Conclusions: These real-life results confirmed lorlatinib as a major treatment option for patients with advanced refractory ALK or ROS1+ NSCLC. READ ARTICLE

Journal of Clinical Oncology DOI:10.1200/JCO.2020.38.15_suppl.9615

Authors: Simon Baldacci, Virginie Avrillon, Benjamin Besse, Bertrand Mennecier, Michael Duruisseaux, Julien Mazieres, Renaud Descourt, Helene Doubre, Pascale Dubray-Longeras, Jacques Cadranel, Denis Moro-Sibilot, Charles Ricordel, Sigolène Galland-Girodet, Isabelle Monnet, Josiane Otto, Sophie Schneider, Pascale Missy, Franck Morin, Virginie Westeel, Nicolas Girard

ALK immunohistochemistry positive, FISH negative NSCLC is infrequent, but associated with impaired survival following treatment with crizotinib

Objective: Metastasized non-small cell lung cancer (NSCLC) with an anaplastic lymphoma kinase (ALK) rearrangement is usually sensitive to a range of ALK-tyrosine kinase inhibitors. ALK-positive NSCLC have been identified in pivotal phase III trials with fluorescence in situ hybridization (ALK FISH+). These tumors are also expressing the fusion product (ALK immunohistochemistry (IHC)+). However, discrepant cases occur, including ALK IHC + FISH-. The aim of this study was to collect ALK IHC + cases and compare within this group response to crizotinib treatment of ALK FISH + cases with ALK FISH- cases. Conclusion: ALK IHC + FISH- NSCLC is infrequent and associated with a worse outcome on personalized treatment. A suitable predictive testing strategy may be to screen first with IHC and then confirm with FISH instead of considering ALK IHC equivalent to ALK FISH according to the current guidelines. READ ARTICLE

Lung Cancer DOI:10.1016/j.lungcan.2019.09.023

Authors: E. Thunnissen, B.I. Lissenberg-Witte, M.M. van den Heuvel, K. Monkhorst, B.G. Skov, J.B. Sørensen, A. Mellemgaard, A.M.C. Dingemans, E.J.M. Speel, A.J. de Langen, S.M.S. Hashemi, I. Bahce, M.A. van der Drift, M.G. Looijen-Salamon, J. Gosney, P.E. Postmus, S.M.S. Samii, F Duplaquet, B. Weynand, X. Durando, F. Penault-Llorca, S. Finn, A.O Grady, B. Oz, N. Akyurek, R. Buettner, J. Wolf, L. Bubendorf, S. Duin, I. Marondel, L.C. Heukamp, W. Timens, E.M.D. Schuuring, P. Pauwels, E.F. Smit